SCOR Project #3 (Bandstra) relates to the overall Center and the preclinical projects in that it examines an important women's health problem (addiction and related disorders) from an interdisciplinary approach over the lifespan from gestation through adolescence, and ultimately, adulthood. The study seeks to answer important questions about previously understudied hypothesized sex and gender differences in drug involvement through late adolescence as well as the outcomes of female (versus male) offspring exposed to drugs in utero. The project emanates from a well-established research program on perinatal substance abuse. Participants (lowSES, inner-city African American infants and their mothers) were enrolled at delivery (n=476) and have been assessed for developmental, neuropsychological, educational, and social- environmental outcomes through early adolescence (retention 85%). Within a developmental model allowing for multiple determinants of behavior and health, this project seeks to estimate male-female differences in progression through levels of adolescent drug involvement, with examination of hypothesized mediators and correlates including stress/coping, internalizing/externalizing behaviors, impulsivity and risk-taking propensity. The influence of in utero cocaine exposure on observed male-female differences will be assessed. Subjects will be tested at ages 16 and 18 by self-report and biomarkers for drug involvement, caregiver and self-report of psychosocial risk factors, and measures of stress reactivity (with salivary cortisol), risk-taking, and decision-making. Benefiting from data from a related K01, the study will have 4 waves of data on drug involvement from ages 12-18 years for analyses with a sex/gender focus and linkage to earlier data on in utero and longitudinal measurements (e.g., neuropsychological functioning, internalizing and externalizing behaviors). Findings should undergird future planned serial assessments of drug involvement into adulthood, when drug dependence among women during child-bearing years is anticipated to be more prominent, endangering their health and that of their offspring. The ultimate goal is enhanced understanding of the differential effects of drugs of abuse in females and males across development (from prenatal to postnatal exposures during adolescence and adulthood), resulting in improved sex-, gender-, and age-specific preventions and treatments for drug addiction and related conditions.